EA021036B1 - Improved apparatus for the aerosolization of large volumes of dry powder - Google Patents

Abstract

The invention relates to a device (1) for dosing and aerosolization of aerosolizable material. The device (1) comprises a body (2) with an aerosolization channel (3) with a distal attachment portion connectable to a source of carrier gas which provides pressure pulses to the aerosolization channel (3); a proximal attachment portion (2a) for outputting aerosolized material and a reservoir (9) for receiving aerosolizable material. The reservoir (9) comprises walls (10, 11, 12) and is connected in a gas-tight manner to the body (2) and in fluid connection with the aerosolization channel (3). At least part of the walls of the device (1) are self-exciting membranes that can be put into oscillation by the pressure pulses.

Description

The invention relates to a device for dispensing and aerosolizing aerosolizable dry material, in particular powdered drugs, such as, for example, pharmaceutical preparations for inhalation. The device is particularly suitable for aerosolization of powdered pulmonary surfactant preparations.

State of the art

Devices for aerosolization (dry spraying) of aerosolizable dry material are known to those skilled in the art. For example, in relation to aerosolization of powdered pharmaceutical preparations, so-called powder inhalers, aerosolizing dry powders, have been described. In such devices, an aerosolizable material, for example a powdered drug substance, is exposed to a compressed gas or carrier gas in a specially provided chamber, and inside this chamber the aerosolizable material is transferred to a state called aerosol or dry mist. In this case, the material particles are in the form of a fine suspension, preferably distributed evenly over the entire volume of the compressed gas or carrier gas, and then in this state are discharged from the chamber using appropriate devices.

Such devices can be used to introduce drugs into the body of patients with spontaneous (independent) breathing or patients with mechanical ventilation. For use in patients with spontaneous breathing, these devices are usually connected to the appropriate mouthpiece or breathing mask. For invasive use, i.e. in the case of patients with mechanical ventilation, these devices deliver the aerosolized drug to the artificial ventilation system, which then delivers the aerosolized material to the patient's lungs.

However, the previously known devices for aerosolization of powdered material are inherent in the problem that the delivery of large quantities of medicinal substances to the patient, if possible, is only possible with significant hardware costs, for example, using complex mechanical metering devices. Typically, known devices are suitable for aerosolization of pharmaceutical quantities in the range of from about 1 μg to about 20 mg. Some medicinal substances, such as, for example, preparations of pulmonary surfactants, i.e. surface-active substances of the lung (surfactant), you need to enter into the body in large quantities, for example, exceeding 100 mg, or even in quantities measured in grams, which when using conventional powder inhalers requires inhalation for a very long time. A second problem with prior art devices may be reproducibility of the amount of aerosolized material delivered to a patient. This problem is especially relevant when, during storage of an aerosolizable material or even during operation of an inhaler, particles of an aerosolizable material stick together to larger particles having different aerodynamic characteristics. Large particles have a much lower chance of getting to their destination, deep into the lung, because they tend to settle in the upper respiratory tract or in the larynx or even somewhere in the inhalation apparatus.

The problem of introducing large amounts of aerosolizable material into the body, such as pulmonary surfactant preparations, precisely in the given doses concerns all areas of the equipment used for inhalation: the air supply device and its controller, the aerosolizing unit, the piping system and valves (including the internal surfaces of the artificial ventilation system lungs, if one is provided) and terminal respiratory devices (mask, tube), in other words, all areas in which there may be uncontrolled I aerozolizovannyh loss of particles due to their undesirable deposition, which entails a decrease in the dose delivered to the patient, as well as the blockage of the lumen.

One problem that is usually encountered in the case of conventional aerosolizing units is that the aerosolizable material, which is in the form of a loose charge in a container for storing it, for example in a pharmaceutical bottle on the market, is prone to sticking of its particles, due to the quality of their surface and / or moisture content in it, which can lead to blockage of a relatively narrow passage section of the bottle opening. Such adhesion is also subject to pulmonary surfactant preparations. Such blockages are usually eliminated only by suitable mechanical means used to ensure continuous dosing of the aerosolizable material over a long, long period of time. In addition, as noted above, adherent particles of aerosolizable material, such as pulmonary surfactant preparations, are usually unable to penetrate the lungs with the same efficiency and local distribution / deposition pattern as smaller, non-adherent particles.

In a prior art aerosolizing unit disclosed in Publication ABOUT 24848 A, the aerosolizable material reservoir is connected by a narrow passage to a chamber into which air is pumped with a syringe. When air is injected into the reservoir and swirls in the reservoir, the adhered aerosolized particles are separated, after which the dispersed aerosolized material is forced out through the chamber and discharged from the nozzle towards the patient. In the publication RK 2598918 A, the aerosolizable material, in contrast to the previous solution, is fed by an Archimedean screw into a stream of compressed air, where the dispersion of particles occurs.

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In many cases, it is necessary to ensure the rapid introduction into the lungs of a high dose of an aerosolizable material in a form capable of penetrating into the alveoli, while ensuring constant dosage in a rapid burst and within a few minutes. However, both of the aforementioned systems cannot ensure the introduction of high doses of aerosolizable material into the body and, due to their geometry and dispersion mechanism, are still subject to particle sticking, which occurs, for example, in a chamber or in a hopper equipped with an auger, so that precise dosing remains problematic. In fact, such an introduction, if at all possible, was only with significant hardware costs.

UO 2006/108558 A1 discloses a device for dispensing and aerosolizing a powder in which separation of adherent particles of an aerosolizable material, such as a pulmonary powder surfactant powder, is achieved by compensating for the pressure between pressure pulses sent to the aerosolization channel of the device. The shear force required to separate the adhering particles is created by high pressure during pulses. Although this system surpasses the prior art systems in terms of the delivered concentration of aerosolized material, the problem of adhesion of residues of the aerosolized material to the internal surfaces of the system, such as the surface of the walls of the tank or the lower surface of the aerosolization channel, remains unsolved.

Another problem concerns the output characteristics of the metering device, such as that disclosed in publication UO 2006/108558 A1. Since the metering device uses pressure pulses to separate adhering particles, the question arises of the possible effect of such pressure pulsations on the patient. Pressure pulses are significant, which means that the metering device cannot be directly connected to the patient’s terminal respiratory devices, such as masks in the case of patients with spontaneous breathing. For patients with artificial lung ventilation, the output of the dosing device should be connected to an artificial lung ventilation device to ensure both adequate and accurate dosing, as well as the supply of the required amount of oxygen. In addition, in the case of young children, the volume and dosage of the supplied aerosol, as well as the partial pressure of oxygen and airway pressure are even more critical than in adults, and require special attention. Since in the case of young children, the usual approach to delivering air-weighed drugs through pressure transmitting respirators and tubes creates an extremely high load on the body, this requires specialized equipment and facilities.

Disclosure of invention

Thus, the aim of the present invention is to provide a device for dispensing and aerosolizing aerosolizable dry material, which would overcome the above problems of the presence of residues of aerosolizable material and would provide aerosolization and delivery to the patient almost all of the aerosolizable material available in the device, thereby ensuring previously not achieved dosing accuracy also when it is necessary to introduce large volumes of dry powder into the body.

Since the scope of the device according to the invention is not limited to the dosage and aerosolization of medical substances, such as substances used for diagnostics and / or treatment, another objective of the invention is to provide a device for dispensing and aerosolization of aerosolized dry material, which would overcome the described above the problem of the presence of residues of aerosolizable material and would provide aerosolization of almost all available aerosolizable material in the device .

Another objective of the invention is to create a system for dispensing and aerosolizing aerosolized dry material, which would provide the possibility of treating patients with spontaneous breathing, as well as with mechanical ventilation, and could be used for both adults and children.

These goals are achieved by means of a device for dispensing and aerosolizing aerosolizable dry material described in claim 1. Particular and preferred embodiments of the invention are described in the corresponding dependent claims.

The first object of the invention is a new device for dispensing and aerosolizing aerosolizable dry material, which contains a housing with an aerosolization channel having a distal connecting part connected to a source of a pulsating carrier gas stream supplying gas pressure pulses to the aerosolizing channel, and a proximal connecting part for outputting the aerosolized material (aerosol) towards the patient, as well as a reservoir for placing aerosolized material (terms proximal and di experimentally used in the context of the invention with respect to the patient, i.e. both the proximal and distal to the patient from the patient). Preferably, the device also has a connecting section connected to a source of non-pulsating carrier gas stream, which serves to transport the resulting aerosol from the aerosolization channel or from the reservoir towards the patient. The tank has walls, is hermetically connected to the body and communicates with the aerosolization channel. At least part of the walls are membranes driven by vibrational motion. Although the latter can be implemented by any type of actuator, it is preferable that the membranes are self-excited membranes driven in oscillatory motion by pressure pulses.

Preferably, the proposed new device contains means for transmitting vibrational energy between different zones of the membranes. These means can advantageously utilize the energy of vibrations excited by pressure pulses. The vibrational energy is preferably transferred from the stronger oscillating zones of the membranes to the weakly oscillating zones. This allows you to equalize (compensate) the pressure difference between the membranes, thus activating, weaker oscillating zones. Such a transfer of energy can be realized, for example, using a tube connecting the proximal connecting part and / or the aerosolization channel and the distal reservoir of the device.

A membrane in the context of the invention is understood to mean any sheet-like structure impervious to gas, liquid and aerosolizable material and forming at least a portion of the shell holding the aerosolizable material in the tank. The term “self-excited” refers in the context of the invention to the property of a membrane to elastically deform and oscillate (vibrate) in response to pressure pulses of the carrier gas supplied to the device. In this regard, it should be borne in mind that, depending on the material of the membrane, the membrane must be thin and flexible enough to deform under the influence of pressure pulses. Elastic polymers such as silicone may be mentioned as examples of membrane material, but other materials will also be apparent to one skilled in the art.

Due to the fact that the device according to the invention is provided with walls made in the form of membranes (membrane walls), it is able to use almost all the amount of aerosolizable dry material stored in the tank and turn it into an aerosol, since the oscillations of the membrane walls of the tank whip and loosen the aerosolizable material, which allows it fall into the dosing chamber under the tank. The aerosolization process is described, for example, in the publication \\ 'O 2006/108558.

Thus, the invention allows after each pressure pulse to be located in the device for dispensing and aerosolizing uniformly loose charges of aerosolizable dry material, which eliminates gradually increasing compaction of the material, and uniform dosing is guaranteed for a significant period of time. Thus, the device according to the invention easily allows metering of aerosolizable material in large quantities with a high degree of reproducibility and, preferably, without the use of moving parts. In addition, during pressure equalization between the aerosolization channel and the tank, the charge of the aerosolizable material is loosened. Thus, it becomes possible that the mixture of compressed carrier gas and material contains predominantly separated particles, preferably exclusively or almost exclusively particles, the size of which corresponds to the primary, non-adherent particles of the aerosolizable material. If the aerosolizable material is a powdered drug substance, such as, for example, powdered pulmonary surfactant, it becomes possible that in the mixture of compressed gas and this material primary particles of the drug substance are present in the reservoir. In this regard, the device according to the invention provides, preferably having no mechanical moving parts at all, optimal aerosolization of the aerosolizable dry material, even breaking the lumps of particles to the size of the primary particles.

In the preferred case when the device according to the invention is used for dispensing and aerosolizing substances intended for therapeutic and / or diagnostic purposes, the size of the primary particles of the aerosolizable material preferably corresponds to the average mass aerodynamic diameter (ΜΜΆΌ - abbr. From English words Ф а и и а а а)))) . whose value is such that particles are able to penetrate into the lungs, i.e. get into the place of their action in the respiratory tract or in the alveoli of the lungs. The ΜΜΆΌ value of particles that can penetrate into the lungs is in the range from 1 to 5 microns. Therefore, according to the invention, the desired range of ΜΜΆΌ particles in a mixture of compressed gas and material is from 1 to 5 μm.

It is preferable that a funnel-shaped part tapering to the aerosolization channel be provided in the housing between the reservoir and the channel, and that the walls of the funnel-shaped part are self-excited membranes. The funnel-shaped part is where the aerosolizable material from the tank falls and collects before it enters the aerosolization channel. The pressure differential pulses resulting from the passage of pressure pulses using the Venturi principle create a pressure gradient that ensures the absorption of the aerosolizable material into the aerosolization channel and the capture of this material by the carrier gas stream, which creates a highly concentrated aerosol. Since the walls of the funnel-shaped part are self-excited membranes, the material collected in the funnel-shaped part does not stick to its walls, and almost all of this material can be carried away by the carrier gas.

The reservoir is preferably provided with a lid containing a membrane facing the reservoir.

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If the lid as such allows you to fill the tank and replenish it, then the membrane on the lid will also oscillate and contribute to the complete separation of the adhered particles of aerosolizable material and their separation from the inner surfaces of the tank. If desired, an absorber of gases and / or moisture can be placed between the membrane and the cover.

Additionally, a self-excited membrane can be provided as part of the bottom (bottom wall) of the aerosolization channel under its connection with the tank. When the aerosolizable material falls into the aerosolization channel, not always all this material is immediately carried away by the carrier gas flow and part of the material may settle and collect under the said compound. Due to the fact that this zone is equipped with a self-excited membrane, pressure pulses sent through the aerosolization channel excite this membrane, causing it to oscillate, as a result of which the settled material is trapped by the carrier gas. This configuration can be called a passive control membrane. It is also possible to install a drive (actuator) connected to the membrane in such a way as to bring the membrane into oscillatory motion. In this case, we are talking about active management.

Finally, it is preferable that the tank and the housing are made in one piece. The advantage of this is the possibility of creating a disposable device, which contains the full dose of aerosolizable material is carefully controlled by the manufacturer, and the introduction of contaminants and incorrect dosage due to inaccurate filling of the tank can be eliminated.

The second object of the invention is a system for dispensing and aerosolizing aerosolizable dry material, including the device described above for dispensing and aerosolizing aerosolizable dry material. In addition, with the proximal connecting part of the device for dispensing and aerosolizing the aerosolizable material, a first hollow expander is connected, having a distal part with inner walls tapering towards the proximal connecting part of the device, and a proximal part with inner walls tapering towards the patient, between the distal and proximal parts of the first hollow expander is preferably located a Central cylindrical part.

Under the extender in the context of the invention is meant an additional element of the gas path through which breathing gas or carrier gas / aerosol passes and which introduces space into the path for the expansion of the pulsating gas flow. The geometry of the first hollow expander provides the suppression of a gas pressure pulse carrying an aerosol to the patient, and at the same time reduces the noise associated with this, and the expander acts in much the same way as a silencer. Thus, in the case of patients with spontaneous breathing, and in the case of patients with mechanical ventilation, the aerosol flows to the patient more evenly and without unacceptable pressure surges.

According to a preferred embodiment of the invention, the inner walls of the distal part, the central part and / or the proximal part of the first hollow expander contain self-excited membranes. When the differential pressure impulse (excess pressure impulse) enters the system, the membranes, due to their elasticity, oscillate, which helps to prevent particles from the aerosol from sticking to the walls of the expander, because of which adhering particles remain on the walls.

It is also preferable that between the distal and Central parts of the first hollow expander was provided annular gap connected to the source of auxiliary air. In this annular gap, auxiliary air can be supplied, washing the expander from the inside and not allowing the aerosolizable material to remain in the expander, sticking to its wall. Most preferably, the geometry of the annular gap provides for the formation of a protective stream of auxiliary air along the walls of the cylindrical part of the expander, thereby enclosing the aerosol stream entering the expander into the air shell and effectively helping to avoid the deposition of aerosolized particles on the expander walls.

In a preferred embodiment of the invention, the system according to the invention also includes a second hollow expander attached to the proximal part of the first hollow expander and distally to the connector on the patient side, and at the distal end of the second hollow expander an inlet with a check valve for atmospheric air is provided, and proximal end - exit for exhaled gas. The second hollow expander preferably has a larger cross-section and volume than the aforementioned first hollow expander, and in a preferred embodiment may be cylindrical, although the invention does not impose limitations on its shape.

This arrangement is particularly advantageous for administering aerosolized material to patients with spontaneous respiration. Like the first hollow expander, the second hollow expander is used to damp the differential pressure pulses from the compressed air source and passing through the metering and aerosolization device, as well as to reduce the noise associated with them. At the same time, it also serves as a container, or receiver, for intermediate storage of aerosol, i.e. aerosolized material suspended in a carrier gas. From this receiver, which is connected to the mouthpiece of the patient, a patient with spontaneous breathing can inhale a predetermined dose of aerosolized material. Due to the expansion of the second hollow expander in cross section and its larger volume with respect to the first hollow expander, the negative respiratory pressure (vacuum), which must be created to draw in and inhale the aerosolized material from the second hollow expander, does not become excessive, as would be the case if the metering and aerosolization device and the first hollow expander were directly connected to the patient. In addition, the inhalation of aerosolized material from the first or second expander is further facilitated by the supply of auxiliary air described above.

In an alternative preferred embodiment of the invention, the aerosolization device is connected to an artificial lung ventilation system that operates as a system for maintaining a constantly positive airway pressure (CPAP, English abbreviated CPAP from soyiiioik rokuyue ayuau rgekkig) and providing the patient with respiratory support in the form of assisted ventilation . In such an installation, the aerosol is introduced into the artificial lung ventilation system or into the PPAP maintenance system through a tee (T-shaped connector) leading to the patient's terminal respiratory device. This system provides numerous benefits for patients undergoing mechanical ventilation or assisted ventilation, especially for young children and newborns. In emergency situations, these small patients may need carefully controlled administration of aerosolized drugs. By connecting an artificial lung ventilation device or a PPAP support system and a dosing and aerosolization device via a tee (T-shaped connector), which connects the device of the invention in parallel with the respiratory support device, it is possible to control how much air or oxygen is supplied to the patient by the mechanical ventilation device (by controlling air pressure and / or oxygen), and separately by the amount of aerosolized material supplied to the patient la In addition, unlike the supply of an aerosol to the respiratory gas branch of the ventilator, this configuration allows the patient to be delivered with an aerosol at higher concentrations of aerosol in the gas, since aerosol dilution is minimized.

As mentioned above, means may be provided for transmitting vibrational energy from one zone of the membranes to another.

Preferably, between the inner space of the first hollow expander and the inner space of the funnel-shaped part was provided equalization (compensation) tube. This tube serves to equalize the pressure differences between the expander and the reservoir and at the same time to activate the funnel-shaped membrane.

The systems described above can be integrated into standard mechanical ventilation systems for regular administration to the body or the addition of aerosolizable material such as pulmonary surfactant to the respiratory gas.

It will be apparent to those skilled in the art that the aerosolization apparatus described above can be used in a wide variety of technical fields. In fact, the device according to the invention will be applicable wherever effective and uniform aerosolization of powders is required. Although preferred applications of the device of the invention are in the field of therapy and administration of inhaled drugs, pharmaceuticals and other drugs, in particular pulmonary surfactant, this device will be useful for aerosolization of any kind of aerosolizable substances in amounts ranging from less than 100 mg to several grams of the substance. It is even possible that when performing the device of the invention in an embodiment having an appropriate size, it will allow aerosolization of substances in even larger quantities, up to an industrial scale. The particle size or particle size distribution of the material to be aerosolized will depend on the particular application. For example, as is known in the art, particles that are to be introduced into the lung by inhalation should ideally have a size ΜΜΆΌ in the range of 1-5 microns. Of course, the possibilities of using the device of the invention are not limited to aerosolization of particles with sizes in this range of values. On the contrary, for aerosolization by using this device, both smaller and larger particles are suitable. As an example, a possible application of the invention may be the application of a powder coating to the processed products, which has become important in recent years and in which relatively large quantities of particles having a very small size (for example, <1 μm) must be aerosolized.

Accordingly, the present invention relates to a device for dispensing and aerosolizing an aerosolizable material, comprising a housing with an aerosolization channel having a distal connecting part connected to a carrier gas source supplying gas pressure pulses to the aerosolization channel, and a proximal connecting part for discharging the aerosolized material towards to the patient, an aerosolizable material storage tank having walls, hermetically connected to the body and communicating with the channel aerosolization, characterized in that at least part of the walls of the membrane is a self-excited, an oscillatory motion actuated pressure pulses.

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The present invention also relates to the device described above, in the housing of which a funnel-shaped part is provided between the reservoir and the aerosolization channel, which tapers towards the aerosolization channel, the walls of the funnel-shaped part being self-excited membranes.

The present invention also relates to any of the devices described above, wherein the reservoir is provided with a top cap, wherein the top cap contains a self-excited membrane facing the reservoir.

The present invention also relates to any of the devices described above, in which a self-excited membrane is provided in the wall of the aerosolization channel under its connection with the reservoir.

The present invention also relates to any of the devices described above, in which the tank and the housing are integrally formed.

The present invention also relates to any of the devices described above, in which the reservoir is connected to the aerosolization channel through a valve. In one embodiment, the valve is a rotary valve.

Thus, the present invention uses the energy of a pressure pulse generated, for example, by expansion of a compressed gas, to excite elastic elements. As mentioned above, these elements can be membranes, especially self-excited membranes. The excitation of the membranes takes away the energy of the initially created pressure impulse, thereby weakening this pressure impulse. As a result, the aerosolizable material is aerosolized in a more continuous, constant, and uniform manner compared to the rapid discharge caused by an unreduced pressure pulse. Thanks to such a weakening of the pressure pulse, the patient becomes more comfortable breathing the prepared aerosol.

Additionally, the sticking of particles of aerosolizable material, especially in the tank, is prevented.

Brief Description of the Drawings

In FIG. 1 is a longitudinal sectional view illustrating an embodiment of a dosing and aerosolization system according to the invention;

in FIG. 2, the dosing and aerosolization system according to the invention is schematically presented in an embodiment for use with adult patients with spontaneous breathing;

in FIG. 3, the dosing and aerosolization system of the invention is schematically represented in an embodiment for use with young children with mechanical ventilation;

in FIG. 4, the dosing and aerosolization system of the invention is schematically presented in an embodiment for use with adults with mechanical ventilation.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

In FIG. 1 shows a view in longitudinal section of the dosing and aerosolization system of the invention in the first embodiment. System 100 includes a metering and aerosolization device 1, within the housing 2 of which an aerosolization channel 3 is located. At its distal end (on the right in FIG. 1), the housing 2 has a socket 4 in which a capillary tube holder 14 is mounted, which serves as a support for the capillary tube 13. This capillary tube holder 14, in turn, can be connected via connecting lines and a valve ( both are not shown in the drawing) to a source, or supply device, of a pulsating compressed carrier gas. At its proximal end (in Fig. 1 on the left), the aerosolization channel 3 passes into the scattering nozzle 5, the cross section of which continuously increases in the direction from the capillary tube 13.

Above the aerosolization channel 3, a reservoir 9, which is part of the device 1, is located to accommodate the powder material to be aerosolized. The reservoir 9 has an outer wall 10 and an inner part having a cylindrical wall 11 and a tapered wall 12. The walls 11 and 12 are self-excited membranes made, for example, of medical silicone, and have a thickness of about 0.5 mm. Between the outer wall 10 and the cylindrical and conical walls 11 and 12, gaps 6 and 7 are formed, respectively. At the bottom of the tank 9 forms an opening 19 located above the aerosolization channel 3, partially integral with the metering chamber 8. Above this hole 19 is a charge of the powder to be aerosolized (not shown in the drawing), which can be caked to such an extent that it is in the aerosolization channel 3 practically no particles of aerosolizable material will fall. In order to prevent particles from falling into the chamber 8 and thus block the reservoir, the entire structural unit, consisting of parts 5, 3, 15, 8, 13, and 4, can be rotated 90 ° relative to the longitudinal axis of the apparatus. Accordingly, the specified node together with the housing 2 forms a rotary valve, allowing to interrupt the flow of powder stored in the tank 9 into the metering chamber 8 and the aerosolization channel 3.

A lid 16 is provided at the top of the tank 9 to close the tank. A self-excited membrane 17 facing the reservoir is provided on the bottom side of the lid, sealing the upper opening of the reservoir 9. An absorber 18 installed in the lid is located above the membrane

- 6 021036 moisture (or in the general case of gases), eliminating residual moisture or other minor gas impurities in the tank, which otherwise could have a harmful effect. In addition, a gap is formed between the membrane 17 and the moisture absorber 18 (not shown in the drawing).

In this embodiment, the reservoir 9 and the housing 2 with the aerosolization channel 3 are made in one piece, which guarantees complete tightness (gas impermeability) and sterility. However, it should be borne in mind that they can also be individual structural elements that are hermetically fitted to each other.

The scattering nozzle 5 extends into the proximal connecting part 2a, which is integral with the housing 2. On the connecting part 2a, a hollow expander 20 is sealed. The expander 20 has a cylindrical outer wall 21, the distal part with conical inner walls 22, tapering in the distal direction, the proximal part with conical inner walls 24 tapering in the proximal direction, and the central part with cylindrical walls 23 located between the distal part and the proxy small part. As in the case of the reservoir, the walls 22, 23, 24 of the expander 20 are self-excited membranes made, for example, of silicone. Between the outer wall 21 and the walls 22, 23, 24 there are corresponding gaps 25, 26, 27. An annular gap is formed between the distal and central parts of the expander 20, which is connected to the auxiliary gas source (not shown in the drawing).

During operation of the device, pressure pulses of the carrier gas enter the aerosolization channel 3 of the device 1 through the capillary tube 13 and, due to the pressure differential between the gas at the outlet of the capillary tube 13 and the reservoir 9, the aerosolizable material is absorbed by the Venturi principle from the reservoir 9 into the channel 3 aerosolization, dispersed in the carrier gas and carried away by it. At the same time, this differential pressure pulse also acts on the membrane walls 11, 12 of the reservoir 9 and on the membrane walls 22, 23, 24 of the expander 20, causing them to bend and oscillate in accordance with the frequency of the pressure pulses. Thus, the aerosolizable material adhered to the walls returns to the bulk of the material and can freely enter the carrier gas stream.

It should be borne in mind that in alternative embodiments of the invention in the form of self-excited membranes can be made only some of the inner walls of the device. For example, in one alternative embodiment of the invention, only the tapering wall 12 is a self-exciting membrane. It is obvious that each inner wall of the device, which is not made in the form of a self-excited membrane, does not require a gap in the form of a hollow space between this inner wall and the corresponding outer wall. For example, if only a tapering wall 12 is made in the form of a self-exciting membrane, gaps 6 and 25-27 can be dispensed with.

The amount of aerosolizable material that can be introduced into the body using the devices and systems proposed in the invention exceeds 50 mg, and this amount is combined with high dosing accuracy. On the one hand, high metering accuracy allows the use of medicinal substances having a very narrow therapeutic window, and on the other hand, large volumes of aerosolizable material make the system suitable for use with substances that must be administered in large quantities. For example, aerosolizable medicinal substances that can be introduced into the body using the device of the invention include, in addition to pulmonary surfactants, antibiotics, nucleic acids, retard forms (sustained release forms), peptides / proteins, vaccines, antibodies, insulin, osmotically active substances such as mannitol, hydroxyethyl starch, sodium chloride, sodium bicarbonate and other salts, enzymes (e.g. deoxyribonuclease), Ν-acetylcysteine, etc.

In FIG. 2 shows an embodiment of a dosing and aerosolization system 200 used for inhalation of large volumes of dry powder by patients with spontaneous respiration. The system 200 includes the dispensing and aerosolization device 1 and the first expander 20 described above as the first embodiment of the invention, the equalizing (compensating) tube 29 connecting the spaces 6, 7 of the reservoir with the spaces 25, 26, 27 of the expander 20 additionally provided. on the intake side, the system 200 includes a controller 50 connected by a compressed air line 51 to a compressed air source 52 (e.g., a hospital compressed air source) supplying compressed air through a main connecting line AI 41 in the device 1 dosing and aerosolization. The main connecting line 41 is connected to the holder 14 of the capillary tube (distal connecting part) of the device 1. The flow of compressed air entering the device is controlled by a high-speed solenoid valve 40, which opens and closes by means of current pulses 43 sent by the controller in such a way as to ensure a certain number, duration and pulse frequency of air pressure. When using the system, compressed air can be introduced automatically by the controller, but it can also be introduced in accordance with the patient’s breathing in such a way as to match the time schedule of aerosolization and the amount of aerosolized material provided in the second expander with the patient’s breathing characteristics.

Auxiliary connecting line 42 supplies a non-pulsating air flow to the annular gap 28 of the expander 20 (the connection of this line is not shown in the drawing), so that the expander is purged to remove residual aerosolizable material. Both connecting lines 41 and 42 are equipped with filters P, preventing undesirable particles from polluting the aerosol.

On the exhaust side, a second expander 30 is connected to the first expander 20. At the same time, an atmospheric air inlet 31 is provided at the distal end of the second expander 30, equipped with a check valve 32. At the proximal end of the second expander 30 there is a direct connector 34 with a mouthpiece 35, and from the direct connector 34 outlet 36 for exhaled gas branches off perpendicularly to it (which can optionally be equipped with a filter P).

In FIG. Figure 3 shows an embodiment of a dosing and aerosolization system, particularly suitable for emergency respiratory therapy of very young children, such as young children and newborns. Some system components that are identical or equivalent to those described with reference to FIG. 1 and 2 are indicated by the same reference numbers and are not considered again. System 300 includes a metering and aerosolization device 1 and an expander 20, as well as a controller 50, which is included in the system in the same way as in the embodiment shown in FIG. 2. A tube 60 of the ventilator is connected to the output of the expander 20, which, in turn, is connected to the first opening of the tee 61. Further, in this embodiment of the invention, the ventilator is provided, which operates in a mode of maintaining constant positive pressure in airway (CPAP) and delivers respiratory gas through the respiratory gas supply line 64 to the manifold 65, maintaining the pressure in the ventilator at a constant level. From the manifold 65, a common ventilation line 62 is connected to the second opening of the tee 61. The third hole of the tee is connected to the nasopharyngeal tube 66 inserted into the baby through the nose so that its end is just above the glottis.

Further, to measure the flow rate of U ₃ gas in a common line 62 at the collector is a flow sensor 67. On the feedback line, the measuring signals of the sensor are sent to the artificial lung ventilation apparatus 70, which directly controls the pressure in line 64 and line 63, adjusting the corresponding flow rates, and thus indirectly regulates the flow rate of U ₃ . By means of such a pressure control, an additional flow from the spray-dispensing device ensures that U ₃ is lowered, as a result of which the pressure, and hence the total gas flow to the child (U ₅ ), is kept constant.

In addition, an oxygen concentration sensor 69 is installed at the third opening of the tee 61, or T-shaped connector, which monitors the oxygen content in the respiratory gas mixture actually delivered to the baby's lungs. On the feedback line, the corresponding measuring signals of the sensor are sent to the artificial lung ventilation apparatus 70, which, together with information about the gas flow rate, receives a complete picture of the properties of the supplied respiratory gas mixture. Then these properties are respectively regulated by the apparatus 70 of artificial ventilation. Thus, turning on the device 1 in parallel with the respiratory support system allows both oxygen-rich breathing gas and an accurate dose of aerosolized material, such as pulmonary surfactant, to be supplied.

Finally, in FIG. 4 shows another embodiment of a dosing and aerosolization system. System 400 is used for adult patients with artificial lung ventilation and includes a dosing and aerosolization device 1, a controller 50, an artificial lung ventilation apparatus 71, and a hollow expander 80. The controller is connected to a hospital air source 52 in the manner described above and connected to the main device 1 connecting line 41 to valve 40 in the same manner as in the above embodiments. However, in this embodiment, expander 80 is made significantly larger in diameter and volume than expander 20, taking into account the needs of an adult patient with mechanical ventilation. At its distal end, expander 80 is connected to the proximal connecting part 2a of device 1, and at its proximal end, it has a direct connector 84 leading to the breathing mask 85. On the side at the distal end of expander 80 is a breathing gas inlet 81 provided with a check valve 82 and connected to the artificial lung ventilation apparatus 71 in a conventional manner through a filter and a respiratory gas supply line 64. Similarly, on the proximal side, there is an exhaled gas outlet 86 connected to the ventilator through a check valve 82 and an exhaled gas return line 63.

The amount of aerosolizable material that can be introduced into the body using the devices and systems proposed in the invention exceeds 50 mg, and this amount is combined with high dosing accuracy. On the one hand, high metering accuracy allows the use of medicinal substances having a particularly narrow therapeutic window, and on the other hand, large volumes of aerosolizable material make the system suitable for use with substances that must be administered in large quantities. For example, aerosolizable medicinal substances that can be introduced into the body using the device proposed in the invention include, in addition to pulmonary surfactants, contrast agents, antibiotics, nucleic acids, retard forms

- 8 021036 (sustained release forms), peptides / proteins, vaccines, antibodies, insulin, osmotically active substances such as mannitol, hydroxyethyl starch, sodium chloride, sodium bicarbonate and other salts, enzymes (e.g. deoxyribonuclease), Ν-acetylcysteine etc.

Claims (20)

CLAIM 1. A device for dispensing and aerosolizing an aerosolizable dry material, comprising a housing with an aerosolization channel, having a distal connecting part connected to a source of carrier gas, supplying gas pressure pulses to the aerosolizing channel, and a proximal connecting part for outputting the aerosolized material towards the patient; a reservoir for accommodating aerosolized material, having walls hermetically connected to the housing and communicating with the aerosolization channel, characterized in that at least part of the walls are self-exciting membranes driven by pressure pulses in an oscillating motion. 2. The device according to claim 1, in the case of which between the tank and the channel of the aerosolization is provided a funnel-shaped part, tapering to the channel of the aerosolization, and the wall of the funnel-shaped part are self-exciting membranes. 3. The device according to claim 1 or 2, in which the reservoir is provided with an upper lid, and the upper lid contains a self-exciting membrane facing the reservoir. 4. A device according to any one of the preceding claims, in which a self-priming membrane is provided in the wall of the aerosolization channel under its connection with the reservoir. 5. Device according to any one of the preceding paragraphs, in which the tank and the housing are made in one piece. 6. A device according to any one of the preceding claims, in which the reservoir is connected to the aerosolization channel by means of a valve. 7. The device according to claim 6, in which the valve is a rotary valve. 8. A system for dispensing and aerosolizing an aerosolized dry material, comprising a device according to any one of claims 1 to 7, in which a first hollow dilator is attached to the proximal connecting part of the said device, having a distal part with inner walls tapering towards the proximal connecting parts of the specified device, and the proximal part with internal walls tapering towards the patient. 9. The system of claim 8, in which between the distal and proximal parts of the first hollow dilator is located the central cylindrical part. 10. The system of claim 8 or 9, in which the inner walls of the distal part, the central part and / or the proximal part of the first hollow dilator contain self-exciting membranes. 11. The system according to claim 9 or 10, in which between the distal and central parts of the first hollow expander provides annular gap connected to the source of auxiliary air. 12. The system according to claim 11, also comprising a second hollow dilator connected by a distal side with a proximal part of a first hollow dilator and a proximal side with a mouthpiece, with an inlet with a check valve for atmospheric air at the distal end of the second hollow dilator, and for proximal the end provides an outlet for exhaled gas. 13. The system according to claim 11, which also includes a ventilator or a valve that maintains constantly positive airway pressure, the proximal part of the first hollow expander and a ventilator or valve that maintains constantly positive airway pressure are connected via a tee end respiratory device of the patient. 14. The system according to claim 13, in which the ventilator provides an air supply opening and an exhaled gas receiving opening connected to said tee by means of a manifold. 15. The system of claim 13 or 14, wherein the patient’s breathing apparatus is a nasopharyngeal tube. 16. A system for dispensing and aerosolizing an aerosolized dry material, comprising a device according to any one of claims 1 to 7, also comprising a hollow expander connected by a distal side with a proximal connecting part of said device, and a proximal side with a terminal respiratory device, and a ventilator, and the expander at its distal end is connected through a non-return valve to the air supply opening of the ventilator, and maximum DUTY end - with the opening reception of the exhaled gas ventilation system. 17. A system according to any one of claims 13 to 16, in which a flow sensor and / or an oxygen concentration sensor is provided between a medical ventilator or a valve to maintain a constantly positive airway pressure and a patient. 18. The system of claim 14 or 15, in which a flow sensor is provided for the collector, and - 9 021036 to the patient of the lateral opening of the tee is provided with an oxygen concentration sensor. 19. A system according to any one of claims 8 to 18, in which an equalizing pipe is provided between the interior of the first hollow expander or hollow expander and the interior of the funnel. 20. A system according to any one of claims 8 to 19, also including a control unit designed to ensure supply to the dosing device and aerosolize pressure pulses of the carrier gas, connected to a hospital source of compressed air, connected to the distal connecting part of the dosing device housing and aerosolization by means of a valve and adapted to control the number and frequency of pressure pulses of the carrier gas and the flow rate of the gas carrier by controlling the indicated valve.